Dietary PUFAs drive diverse system-level changes in lipid metabolism.
Dietary PUFAs drive diverse system-level changes in lipid metabolism.
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DOI：
10.1016/j.molmet.2022.101457
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发表时间：
2022-05
影响因子：
8.1
通讯作者：
Koulman A
中科院分区：
文献类型：
--
作者：
Furse S;Virtue S;Snowden SG;Vidal-Puig A;Stevenson PC;Chiarugi D;Koulman A
多不饱和脂肪酸（PUFA）补充剂已被试验作为一种治疗多种疾病的方法，并产生了各种结果。这种多样性归因于补充剂，通常包含脂肪酸的混合物，以及对不同器官的不同影响。在这项研究中，我们测试了这样一个假设，即补充单个PUFA具有依赖于PUFA分子结构的系统水平效应。我们进行了一个网络分析，使用脂质流量分析，以确定局部和系统水平的脂质代谢的变化，使用公开的脂质组学数据，从小鼠模型补充FA（20：4 n-6），FA（20：5 n-3），和FA（22：6 n-3）;花生四烯酸，二十碳五烯酸，二十二碳六烯酸，分别。脂质运输分析是一种新的计算/生物信息学工具，其使用脂质的空间分布来查明代谢控制的变化或差异，从而提出观察到的脂质代谢差异的机械原因。有强有力的证据表明，脂质代谢的变化是由补充的PUFA的结构驱动和依赖的。磷脂酰胆碱和甘油三酯的变化的品种超过变量的总数，而磷脂酰乙醇胺和磷脂酰肌醇显示了相当大的变化，在这两个变量和它们的数量，在一个高度PUFA依赖的方式。还有证据表明，脂肪酸的内源性生物合成以及脂肪酸的延长和去饱和都发生了变化。这些结果表明，PUFA补充剂的全部生物学影响远远大于任何单一器官效应，并意味着PUFA的补充和给药需要系统水平的评估。PUFA补充剂在补充剂的小鼠模型中驱动系统水平的效应。系统层面的影响只能通过网络分析（如长期评估）获得。脂质的空间分布揭示了变化的机制基础。脂质运输分析是研究脂质代谢机制的理想工具。
Polyunsaturated fatty acid (PUFA) supplements have been trialled as a treatment for a number of conditions and produced a variety of results. This variety is ascribed to the supplements, that often comprise a mixture of fatty acids, and to different effects in different organs. In this study, we tested the hypothesis that the supplementation of individual PUFAs has system-level effects that are dependent on the molecular structure of the PUFA. We undertook a network analysis using Lipid Traffic Analysis to identify both local and system-level changes in lipid metabolism using publicly available lipidomics data from a mouse model of supplementation with FA(20:4n-6), FA(20:5n-3), and FA(22:6n-3); arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, respectively. Lipid Traffic Analysis is a new computational/bioinformatics tool that uses the spatial distribution of lipids to pinpoint changes or differences in control of metabolism, thereby suggesting mechanistic reasons for differences in observed lipid metabolism. There was strong evidence for changes to lipid metabolism driven by and dependent on the structure of the supplemented PUFA. Phosphatidylcholine and triglycerides showed a change in the variety more than the total number of variables, whereas phosphatidylethanolamine and phosphatidylinositol showed considerable change in both which variables and the number of them, in a highly PUFA-dependent manner. There was also evidence for changes to the endogenous biosynthesis of fatty acids and to both the elongation and desaturation of fatty acids. These results show that the full biological impact of PUFA supplementation is far wider than any single-organ effect and implies that supplementation and dosing with PUFAs require a system-level assessment. PUFA supplementation drives system-level effects in a mouse model of supplementation. System-level effects are only obtainable through a network analysis such as LTA. The spatial redistribution of lipids reveals mechanistic bases for changes. Lipid traffic analysis is the ideal tool for mechanistic studies of lipid metabolism.
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